CN1324040C - Medicament for treating diabetes, diabetes complication, its preparation and novel use - Google Patents
Medicament for treating diabetes, diabetes complication, its preparation and novel use Download PDFInfo
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- CN1324040C CN1324040C CNB2003101129280A CN200310112928A CN1324040C CN 1324040 C CN1324040 C CN 1324040C CN B2003101129280 A CNB2003101129280 A CN B2003101129280A CN 200310112928 A CN200310112928 A CN 200310112928A CN 1324040 C CN1324040 C CN 1324040C
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention discloses a medicine for the treatment of diabetes and complications thereof, a preparation method and a new application of the medicine. The present invention is mainly prepared through the steps of grinding and decocting the whole grass of tartary buckwheat, extracting useful components, etc., to obtain total flavonoids of tartary buckwheat which is then prepared into clinically acceptable preparation forms or health food through refining processes, wherein the whole grass of tartary buckwheat refers to the stems, the leaves, the seeds and the shells of tartary buckwheat. The total flavonoids of tartary buckwheat of the present invention has conspicuous curative effect on diabetes and complications thereof.
Description
Technical field
The present invention relates to a kind of medicine or healthcare products, preparation method and new purposes thereof, particularly relate to a kind of pharmaceutical preparation, preparation method and new purposes thereof that contains the Radix Et Rhizoma Fagopyri Tatarici total flavones.
Background technology
Radix Et Rhizoma Fagopyri Tatarici belongs to the polygonaceae dicotyledons, is commonly called as bitter buckwheat, formal name used at school hull buckwheat (F.tataricum).The Radix Et Rhizoma Fagopyri Tatarici happiness is nice and cool, barren-resistant, is grown in high and cold mountain area more, and seed is edible.Be distributed in mountain area, China southwest, the Yi Autonomous Prefecture of Liangshan, Sichuan Province.Compendium of Material Medica record: Radix Et Rhizoma Fagopyri Tatarici nature and flavor hardship, flat, cold, useful strength, continuous spirit, sharp knowledge, the effect that has the wide intestines of sending down abnormally ascending to be good for the stomach.Current clinical medicine is observed and is shown that tartary buckwheat powder and goods thereof have hypoglycemic, regulating blood fat, strengthens the effect of body immunity, and patients such as diabetes, hypertension, hyperlipidemia, coronary heart disease, apoplexy are had treatment or assisting therapy effect.These effects are all relevant with the activeconstituents Radix Et Rhizoma Fagopyri Tatarici total flavones that contains in the Radix Et Rhizoma Fagopyri Tatarici.Bitter in the past foster wheat is studied and mainly is confined to compound and protective foods use, and rare folk prescription uses, and does not see the report and the research of use duck wheat shell and herb, studies then still less for the extraction of its effective constituent.
Diabetes are pathogenic process complexity, restive metabolic disease, and it develops into to a certain degree, can concurrent multiple complication also be complication, and its treatment at present mainly shows as controlling blood sugar and symptomatic treatment.To diabetic complications, especially the capillary blood vessel complication also lacks effective medicine and regulates, and Austria developed first aldose reduction inhibitor agent Doxium in the world in 1971, is mainly used in eye complication in the treatment diabetic microvascular complication.But its activity a little less than, and administration time is usually later, so effect is very not remarkable, 1984, Japan developed another aldose reductase inhibitor according to pool this he, is used for the treatment of the neural complication of diabetic microvascular complication, though its aldose reductase inhibition activity is not strong, terminal illness is not had unusual effect, but active effect is arranged, therefore be widely used in clinically yet for the development of early stage control of diabetes capillary blood vessel complication.The early 1990s U.S. very strong new drug Tolrestat of aldose reductase inhibition activity that goes on the market again, this medicine is early stage to multiple diabetic microvascular complication, significant curative effect is all arranged mid-term, but its liver toxicity is too big, and FDA has to announce to stop using.The domestic still untapped analogous products that go out.
Summary of the invention
One of the object of the invention is to provide a kind of extract of Radix Et Rhizoma Fagopyri Tatarici, i.e. the Radix Et Rhizoma Fagopyri Tatarici total flavones.
Two of the object of the invention is to provide a kind of preparation method and process for purification of Radix Et Rhizoma Fagopyri Tatarici total flavones.
Three of the object of the invention is to provide a Radix Et Rhizoma Fagopyri Tatarici total flavones to make clinically any or pharmaceutically acceptable preparation or protective foods.
Four of the object of the invention is to provide the application of this Radix Et Rhizoma Fagopyri Tatarici total flavones in the medicine of treatment diabetes and diabetic complications.
The extracting method of Radix Et Rhizoma Fagopyri Tatarici total flavones can be selected from a kind of in the following method:
A, with the Radix Et Rhizoma Fagopyri Tatarici herb, i.e. Radix Et Rhizoma Fagopyri Tatarici stem, the Radix Et Rhizoma Fagopyri Tatarici leaf, Radix Et Rhizoma Fagopyri Tatarici (seed), duck wheat shell, powder becomes meal; Add 3～10 times of water gagings, heating decocts, and slowly adds alkaline solution under agitation condition, and water transfer decocting liquid pH value is 7.5～10.5, lixiviate with this understanding, suction filtration while hot; Residue is the same to add 3～8 times of water gagings again, extracts once more as stated above, while hot suction filtration; Merging filtrate adds acid solution, and water transfer decocting liquid pH value is 3～6, leaves standstill after the stirring, filters; Throw out washes with water to neutrality, and drying gets Radix Et Rhizoma Fagopyri Tatarici total flavones crude product.
B, with the Radix Et Rhizoma Fagopyri Tatarici herb, i.e. Radix Et Rhizoma Fagopyri Tatarici stem, the Radix Et Rhizoma Fagopyri Tatarici leaf, Radix Et Rhizoma Fagopyri Tatarici (seed), duck wheat shell, powder becomes meal; Add in the percolator, adding pH value is 10～12 alkali aqueous solution, is dissolved with 0.5～3 ‰ S-WAT in this alkali aqueous solution, and slowly diacolation when the detection percolate does not have chromocor compound, stops diacolation; Percolate adds acid solution, and adjust pH is 2～6; Leave standstill, filter, drying gets Radix Et Rhizoma Fagopyri Tatarici total flavones crude product.
C, with the Radix Et Rhizoma Fagopyri Tatarici herb, i.e. Radix Et Rhizoma Fagopyri Tatarici stem, the Radix Et Rhizoma Fagopyri Tatarici leaf, Radix Et Rhizoma Fagopyri Tatarici (seed), duck wheat shell, powder becomes meal; Add in the refluxing extraction device, add 3～8 times of amount 50～95% ethanol or methanol eddy and extract, extracting liquid filtering reclaims ethanol or methyl alcohol; Crystallization is separated out in refrigeration, filters, and drying gets Radix Et Rhizoma Fagopyri Tatarici total flavones crude product.
D, with the Radix Et Rhizoma Fagopyri Tatarici herb, i.e. Radix Et Rhizoma Fagopyri Tatarici stem, the Radix Et Rhizoma Fagopyri Tatarici leaf, Radix Et Rhizoma Fagopyri Tatarici (seed), duck wheat shell, powder becomes meal; Add 3～10 times of water gagings, decoct and extract, united extraction liquid, extracting solution are behind high speed centrifugation, and being concentrated into relative density is 1.1～1.30 in the time of 50 ℃; Crystallization is separated out in refrigeration, filters, and drying gets Radix Et Rhizoma Fagopyri Tatarici total flavones crude product.
E, with the Radix Et Rhizoma Fagopyri Tatarici herb, i.e. Radix Et Rhizoma Fagopyri Tatarici stem, the Radix Et Rhizoma Fagopyri Tatarici leaf, Radix Et Rhizoma Fagopyri Tatarici (seed), duck wheat shell, powder becomes meal; Add 3～8 times of amount 50～95% ethanol or methyl alcohol, refluxing extraction 1～6 hour; Extracting solution is put to room temperature, and gradation adds gac, stirs, leave standstill, when checking that supernatant liquor does not have the flavones reaction till; Filter, collect the gac of absorption Radix Et Rhizoma Fagopyri Tatarici total flavones, use boiling water successively, the methyl alcohol that boils, 3-10% phenol～aqueous solution, 10-20% phenol～alcoholic solution carries out wash-out; The each several part elutriant is carried out qualitative examination, identify that with PPC most of flavonoid glycoside can wash with 3-10% phenol～aqueous solution; It is 1.2～1.3 in the time of 50 ℃ that elutriant is concentrated into relative density; Residual phenol is removed in the jolting that adds diethyl ether again, remaining water layer concentrating under reduced pressure, and crystallization is separated out in cooling; Filter, drying promptly gets Radix Et Rhizoma Fagopyri Tatarici total flavones crude product.
F, with the Radix Et Rhizoma Fagopyri Tatarici herb, i.e. Radix Et Rhizoma Fagopyri Tatarici stem, the Radix Et Rhizoma Fagopyri Tatarici leaf, duck wheat shell, Radix Et Rhizoma Fagopyri Tatarici (seed), powder becomes meal; Add in the percolator, add 50～95% ethanol, slowly diacolation when the detection percolate does not have chromocor compound, stops diacolation; Percolate filters, and reclaims ethanol to there not being the alcohol flavor; Crystallization is separated out in refrigeration, and filtration, drying get Radix Et Rhizoma Fagopyri Tatarici total flavones crude product.
The process for purification of Radix Et Rhizoma Fagopyri Tatarici total flavones can be selected from a kind of in the following method:
A, get the ethanol of Radix Et Rhizoma Fagopyri Tatarici total flavones crude product of the present invention with boiling water or 50～95%, backflow 1-3 hour, crystallization was separated out in filtered while hot, cooling; Drying promptly gets purified Radix Et Rhizoma Fagopyri Tatarici total flavones.
B, get Radix Et Rhizoma Fagopyri Tatarici total flavones crude product of the present invention and add 2～6 times in water, stirring and evenly mixing slowly adds alkaline solution, and transferring to the pH value is 7.5～10; Add 2～6 times ethanol or methyl alcohol, stir about 1～4 hour filters; Filtrate adds acid solution, and adjust pH is 3～6, fully is heated with stirring to 50～100 ℃, leaves standstill, and filters; Precipitation washes with water; Discard washings, drying promptly gets purified Radix Et Rhizoma Fagopyri Tatarici total flavones.
C, get Radix Et Rhizoma Fagopyri Tatarici total flavones crude product of the present invention and add 2～6 times in water, stirring and evenly mixing slowly adds alkaline solution, and transferring to the pH value is 7.5～10; Stir, filter; Filtrate adds acid solution, and transferring to the pH value is 2～6, fully stirs, and is heated to 50～100 ℃, leaves standstill, and filters; Precipitation washes with water; Discard washings, drying promptly gets purified Radix Et Rhizoma Fagopyri Tatarici total flavones.
D, get Radix Et Rhizoma Fagopyri Tatarici total flavones crude product of the present invention and add 50～95% 1～6 times ethanol, heated and stirred 1～4 hour is filtered, and leaves standstill, and filters, and filtrate adds acid solution, and adjust pH is 2～6, fully is heated with stirring to 50～90 ℃, leaves standstill, and filters; Precipitation washes with water; Discard washings, drying promptly gets purified Radix Et Rhizoma Fagopyri Tatarici total flavones.
Radix Et Rhizoma Fagopyri Tatarici total flavones of the present invention (also claiming the Radix Et Rhizoma Fagopyri Tatarici flavones) comes from Radix Et Rhizoma Fagopyri Tatarici (being the peeling of Radix Et Rhizoma Fagopyri Tatarici seed or Radix Et Rhizoma Fagopyri Tatarici seed), Radix Et Rhizoma Fagopyri Tatarici kind skin (duck wheat shell), the Radix Et Rhizoma Fagopyri Tatarici herb (leaf and the stem that comprise Radix Et Rhizoma Fagopyri Tatarici) of Radix Et Rhizoma Fagopyri Tatarici plant.
Radix Et Rhizoma Fagopyri Tatarici total flavones of the present invention can be made clinically any or pharmaceutically acceptable preparation, comprises oral preparations, as formulation and protective foodss such as tablet, pill, capsule, granule, suspensoid, dripping pill, injection, freeze-dried powders.
The ethanol that uses among the present invention can replace with methyl alcohol or other organic solvents, and methyl alcohol also can replace with ethanol.
The alkaline solution that uses among the present invention can be sodium hydroxide, potassium hydroxide, calcium hydroxide, saturated limewater, Na2CO3, K2CO3 solution; The acid solution that adds can be hydrochloric acid, sulfuric acid, salpeter solution.
The purity that makes the Radix Et Rhizoma Fagopyri Tatarici total flavones with aforesaid method and process for purification can reach more than 95%.The present invention is to the research of Radix Et Rhizoma Fagopyri Tatarici total flavones preparation, prove its stable in properties, quality controllable, evident in efficacy, toxicity is extremely low; Have the nerve conduction velocity of improvement, reduce sorbitol content, increase neural volume of blood flow, increase the quantity of vessel open, suppress thickening of basement membrane of blood vessel, the gsh that reverting diabetes causes reduces, and lipid peroxide raises, and the Na that can raise
+-K
+-ATP enzyme activity, kidney, eye, europathology that diabetes and diabetic complications are caused change the function that obviously alleviates, and the clinical study proof has better curative effect to diabetes and diabetic complications.
Following experimental example is used to further specify the present invention.
Experimental example 1: the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 diabetes rat
Experimental technique:
1, blood sugar and saccharification hemoglobin content are measured: the rat fasting is after 12 hours, and the socket of the eye vein is got blood, and separation of serum is drawn serum 10 μ l, uses the determination of glucose oxidase blood-sugar content.Other gets rat socket of the eye venous blood, and the EDTA anti-freezing is measured glycolated hemoglobin with intelligent blood coagulation analyzer.
2, the mensuration of glucose in urine and urine protein: get rat urine and measure glucose in urine and urine protein content with 8 determinators of urine.
Experimental result:
1, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat model blood sugar: mensuration is respectively organized rat blood sugar before the administration of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule, because U-9889 moulding, the model group rat blood sugar significantly raises than rats in normal control group blood sugar, all the other each treated animal blood sugar and model contrast ratio do not have significant difference, illustrate that each assembly molding situation is identical.Begin administration on this basis, during the administration when the administration of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule finishes, measure again and respectively organize rat blood sugar, the result shows that animal pattern blood sugar significantly raises, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule can make blood sugar significantly descend, than decreasing, there is not significant difference before Radix Et Rhizoma Fagopyri Tatarici total flavone capsule low dose group rat blood sugar and the administration but compare with the model control group rat blood sugar of measuring simultaneously; Before the middle and high dosage group of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule rat blood sugar and the administration than still with model control group than all there being significance to reduce.The hypoglycemic activity of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule presents the doses reaction relation.Control group does not make significant difference to the U-9889 rat blood sugar.
2, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat model glycolated hemoglobin: glycolated hemoglobin can reflect the protein glycosylation level, after U-9889 causes diabetes model, the glycolated hemoglobin of animal significantly raises, rat is taken the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule can make glycolated hemoglobin significantly descend, than decreasing, there is not significant difference before Radix Et Rhizoma Fagopyri Tatarici total flavone capsule low dose group rat glycolated hemoglobin and the administration but compare with the value of the model control rats of measuring simultaneously; Before the middle and high dosage group of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule rat glycolated hemoglobin and the administration than still with model control group than all there being significance to reduce.The Radix Et Rhizoma Fagopyri Tatarici total flavone capsule presents the doses reaction relation to the restraining effect of glycolated hemoglobin.Control group does not make significant difference to U-9889 rat glycolated hemoglobin.
3, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat model sign: experimental session is observed the state of respectively organizing rat, and control rats hair color light, is ingested, drunk water and movable normal at body weight gain.Model group rat hair is fluffy, withered, and weight loss is ingested, the movable minimizing, and drinking-water increases, and male rat begins body weight and obviously reduces around medication the.Radix Et Rhizoma Fagopyri Tatarici total flavone capsule low dose group rat hair is fluffy, and body weight gain is slow, the increase of ingesting, drink water, and activity also reduces.Many rat left eyes have cataract.Along with the prolongation of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule administration time and the increase of dosage, the animal state makes moderate progress, and compares with model control group, and body gets significantly to be increased.Each administration group at medication the 6th all rat body weights than the obvious weightening finish of model group.Middle and high dosage Radix Et Rhizoma Fagopyri Tatarici total flavones group rat does not see that cataract takes place.Some animal hair of control group group is fluffy, ingests, drinks water and movable increase than model control group.During the administration of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule, measure and respectively organize rat body weight, the rat body weight that the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule can make U-9889 cause descends and significantly gos up.Illustrate that the diabetic disease states of animal obviously alleviates after the administration of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule, control group is to the effect that also creates antagonism that descends of U-9889 rat body weight.
4, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat model urine: experimental session is observed the variation of urine amount, glucose in urine and the urine protein of rat.Day urine amount of normal rat is about 13ml, and diabetic model group rat twenty-four-hour urine amount reaches 120ml, and amount of drinking water of rat and urine amount are ten times of normal rat, and fluffy, the withered height of diabetes rat hair, weight loss present multiple typical diabetic symptom.The state of animal takes a turn for the better after the administration of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule, around administration the, measure rat urine amount, model group rat urine amount continues to raise, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule makes the hypourocrinia of rat, the 8th week of Radix Et Rhizoma Fagopyri Tatarici total flavones administration is measured the variation of urine again, and the urine amount of Radix Et Rhizoma Fagopyri Tatarici total flavones administration group rat is near normal level.Glucose in urine and urine protein also present similar variation.Only detect the glucose in urine and the albumen of trace in the control rats, glucose in urine and the urine protein of model group rat significantly increase, and the Radix Et Rhizoma Fagopyri Tatarici total flavones has remarkable antagonistic action to glucose in urine, the urine protein increase of diabetes rat.
Experimental example 2: the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat diabetes complication
Experimental technique:
1, rat coccygeal nerve conduction of velocity is measured: after rat penta horse is anaesthetized than appropriate sodium, place in 37 ℃ of waters bath with thermostatic control fixing, the electricity consumption thorn is measured the coccygeal nerve conduction of velocity, with stimulating electrode be placed on the afterbody near-end, recording electrode is inserted in the afterbody far-end, provide stimulation and record electric potential signal with Pclab bio signal acquisition processing system, stimulate and adopt 5 volts of square waves to stimulate, the wide 0.55ms of ripple, stimulus intervals 3.75ms, calculate the conduction time of stimulus signal, obtain nerve conduction velocity to the distance between the recording electrode divided by conduction time with stimulating electrode to electric potential signal.Plug another recording electrode again, measure distance between two recording electrodes, remove interelectrode distance with stimulus signal by the time of two electrodes and obtain nerve conduction velocity.The average that obtains of calculating is as the nerve conduction velocity of this animal in two ways.
2, the mensuration of sciatic nerve sorbitol content: get rat sciatic nerve, weigh in the rearmounted homogenate pipe, adding distil water 2.0ml prepares homogenate, get supernatant liquor after centrifugal, boil 20min, add 0.2mil/LZnSo40.2ml0.2mol/L Ba (OH) 20.2ml, centrifugation, get supernatant liquor quick concentrate drying in clean tube, add pyridine 0.1ml dissolution residual substance, add silylating reagent BSTFA20 μ l again, shake up, heating 15min, cooling, storing solution 0.3ml in adding.Thereafter get 0.5 μ l and carry out institute's analysis of hplc.Use the perpendicular cuts peak area quantification.Chromatographic condition: 530nm1D5m long capillary chromatographic column, column temperature: 155 ℃ of vaporizer temperature: 250 ℃, sensing chamber's temperature: 250 ℃, N2 flow velocity: 10ml/min, the H2 flow velocity: 20ml/minAIR flow velocity: 20ml/min, attenuation index: 3, sample size: 0.3 μ l.With sorbyl alcohol theory of computation stage number is 393.The detection of sorbyl alcohol is limited to 45.23ng.Regression equation is: Y=0.0077X-0.0527, r=0.9994 (n=6).Concentration range: 0.0167～0.1667 μ g scope internal linear is good, the variation coefficient: 1.75%.Day, within variance coefficient was 1.19%, and the variation coefficient 2.34% in the daytime.The rate of recovery is 100.8%
Experimental result:
1, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat nerve conduction velocity: after applying stimulation with the stimulating electrode of Pclab system, a passage of recording unit records electric potential signal, two passages indication stimulus signal, record nerve conduction velocity.Measure rat coccygeal nerve conduction of velocity respectively before and after the administration of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule, the result shows that the coccygeal nerve conduction of velocity significantly slows down than blank group after the U-9889 moulding, i.e. P＜0.01.And aggravate with the prolongation of moulding time, give the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule on this basis, nerve conduction velocity is improved with the prolongation of administration time, several sections of nerve conduction velocity of Radix Et Rhizoma Fagopyri Tatarici total flavones high dose group rat reach normal control group level, the effect of Radix Et Rhizoma Fagopyri Tatarici total flavones is certain dose-response relationship, and prompting Radix Et Rhizoma Fagopyri Tatarici total flavones has significant antagonistic action to the neural function infringement that diabetes cause.
2, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat sciatic nerve sorbitol content: the standard diagram of gas chromatography determination rat sciatic nerve sorbitol content and sample determination collection of illustrative plates, rat sciatic nerve sorbitol content when finishing with this systems measurement Radix Et Rhizoma Fagopyri Tatarici total flavone capsule administration, the result shows, the refreshing sorbitol content of U-9889 rat model ischium obviously raises, three dosage of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20-80mg/kg all can significantly reduce and pears alcohol level, and are certain dose-response relationship.
Experimental example 3: the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat microcirculation function
Experimental technique
1, the mensuration of rat sciatic nerve volume of blood flow: rat separates left leg sciatic nerve with the anesthesia of 35mg/kg vetanarcol, and nerve is embedded in the plastics groove, and the 1cm place measures the volume of blood flow in the sciatic nerve-trunk that exposes with doppler flowmeter on state's nest.The neural volume of blood flow numerical value of its mean value as this rat is got in the variation of 10 volume of blood flows of continuous recording.
2, rat mesentery micro-cycle measurement: rat is anaesthetized with the 35mg/kg vetanarcol, pull out the epimere jejunum, with the microscopical camera lens of center aligned of first loop of jejunum mesentery, examine under a microscope not the mesentery circulation of rat on the same group, count every square millimeter in visible vascular strip number.
Experimental result:
1, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat sciatic nerve volume of blood flow: measure volume of blood flow in the sciatic nerve-trunk that exposes with the multispectral blood flowmeter of reining in, write down the variation of instantaneous volume of blood flow, get the volume of blood flow data of its mean value, handle by statistics again and calculate neural volume of blood flow as every animal.Measurement result shows: U-9889 diabetes model rat sciatic nerve volume of blood flow obviously reduces, three dosage of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20-80mg/kg all can significantly increase neural volume of blood flow, the neural volume of blood flow of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule high dose group rat even reach the normal rat level.
2, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the microcirculatory influence of U-9889 rat mesentery: examine under a microscope not the mesentery microcirculation of rat on the same group, count every square millimeter in visible vascular strip number, the open frequency of reflection capillary vessel.The result shows that the open bar number of diabetes model rat aorta obviously reduces, and three dosage of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20-80mg/kg all can significantly increase the quantity of diabetes rat vessel open.
3, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat model sciatic nerve basement membrane of blood vessel: visible body spare axon and intranueral capillary blood vessel on the diabetic sciatic nerve HE staining section, the model group vessel wall is thicker, vascular occlusion.The inaccessible phenomenon of visible vessels on the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20mg/kg dosage group HE karyomit(e), the dosage group is also shown in wall of micrangium and thickens in the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule, and the vascular occlusion phenomenon does not appear in high dose group.The visible vessels wall slightly thickens on the HE karyomit(e) of control group, also sees inaccessible phenomenon.
Morphology of microvasculature of infant changes in the sciatic nerve in order further to observe, and adopts the painted basement membrane of blood vessel of 6 amine silver staining selectivity, variation that can clear view capillary blood vessel basilar membrane.Select the capillary blood vessel of diameter between 10 microns big 50 microns, every group of sciatic nerve 6 amine silver staining section that selects 5 animals, observe wherein 10 blood vessels, get 4 points at every blood vessel of microscopically by the intersection point of X-Y axle, measure the thickness of capillary blood vessel basilar membrane, get the thickness of its mean value as this basement membrane of blood vessel.The visible normal control group of result capillary blood vessel basilar membrane place dyes slight black, its thickness between the 0.2-0.8 micron, with 0.8 micron be the boundary, think normal base film thickness below 0.8 micron, think basement membrane thickened more than 0.8 micron.Model control group blood vessel big area is dyed black, and basement membrane of blood vessel thickens than control group is obvious, and normal blood vessels only accounts for 5%, with normal group than p＜0.01, thrombus appears in blood vessel, the vessel wall uneven thickness, the tunica intima border is uneven.Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20mg/kg dosage group basement membrane of blood vessel slightly thickens, and normal blood vessels accounts for 30%, with model group than p＞0.05.Dosage group capillary blood vessel basilar membrane slightly thickens in the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule, and normal blood vessels accounts for 93%, with model group than p＜0.01, illustrate that the state of blood vessel is significantly improved.The thickness and the normal control of high dose group basement membrane of blood vessel are approaching, and do not see the vascular occlusion phenomenon.Control group group visible vessels wall slightly thickens, and base film thickness and model group significantly reduce, and normal blood vessels accounts for 60%-70%, with model group than p＜0.01.Above presentation of results Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the restraining effect that thickened of U-9889 rat model sciatic nerve basement membrane of blood vessel.
Experimental example 4: the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat biochemical indicator
Experimental technique:
1, the brain glutathione content is measured: with the rat sacrificed by decapitation, get brain 0.2g in ice bath, phosphate buffered saline buffer and 10% trichoroacetic acid(TCA) 0.8ml with 0.1mol/L pH8.0 make 10% homogenate, 4000rpm is centrifugal 15 minutes under the room temperature, separation of supernatant 0.5ml, the phosphate buffered saline buffer 4.5ml dilution that adds 0.1mol/L pH8.0, add 0.4g/L DTNB test solution 0.02ml, mixing, not add the control tube zeroing of brain homogenate, with 721 spectrophotometer 412nm wavelength place colorimetrics, absorbance goes out every Borneo camphor divided by the brain recuperation and organizes contained gsh amount after 5 minutes.
2, brain lipid peroxide (MDA) assay: with the rat sacrificed by decapitation, get brain and make 10% homogenate with the 0.05mol/LpH7.4 phosphate buffered saline buffer, add 8.1%SD0.2ml successively, the acetate buffer solution 1.5ml of pH3.5,1%TBA1.5ml, distillation water-bath 40 minutes, centrifugal 15 minutes of cooling back 3000rpm, get supernatant liquor, 721 spectrophotometer 532nm wavelength places measure absorbancy, absorbancy is gone out every Borneo camphor divided by the brain recuperation organize contained MDA amount.
3, brain Na+-K+-ATP enzyme assay: with the rat sacrificed by decapitation, get brain and make homogenate, directly add in the enzyme reaction pipe each compound concentrations NaCL100mmol/L in the reaction solution with rough homogenate with 0.2mmol/LTris-HCL damping fluid (pH7.4); MgCl22.5mmol/L; KCL10mmol/L; EDTA1.0mmol/L; Reaction is 30 minutes in 37 ℃ of water-baths of ATPNa21.0mmol/L or ouabain 0.2mmol/L, speed adds inorganic phosphorus developer 2.5ml and (contains 0.02% Victoria Green WPB, 0.55% ammonium molybdate and 0.1% polysorbas20) add 2.4% Trisodium Citrate 0.2ml again, room temperature reaction 30 minutes, 721 spectrophotometer 660nm wavelength places measure absorbancy, calculate content of inorganic phosphorus, Na
+-K
+-ATP enzyme bad temper for do not contain because of with the difference that contains ouabain two pipes, go out every Borneo camphor divided by the brain recuperation and organize contained Na
+-K
+-ATP enzyme activity unit.
Experimental result:
1, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat brain group glutathione content: next day after the administration of U-9889 diabetes rat last, get the rat akrencephalon and measure and respectively organize rat glutathione (GSH) content.The result shows that diabetes model rat GSH content obviously reduces, and control group can stop the reduction of GSH, and three dosage of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20-80mg/kg all can significantly increase diabetes rat GSH content, and are certain dose-response relationship.
2, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat cerebral tissue lipid peroxide content: next day after the administration of U-9889 diabetes rat last, get the rats with left skin and measure lipid peroxide (MDA) content, the result shows that diabetes model rat MDA content obviously raises, three dosage of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20-80mg/kg all can significantly reduce diabetes rat MDA content, and are certain dose-response relationship.
3, the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the Na of U-9889 rat cerebral tissue
+-K
+The influence of-ATP enzyme activity: next day after the administration of U-9889 diabetes rat last, get rat right side cortex and measure Na
+-K
+-ATP enzyme content.The result shows diabetes model rat Na
+-K
+-ATP enzyme content obviously reduces, and three dosage of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20-80mg/kg all can significantly increase diabetes rat Na
+-K
+-ATP enzyme activity, and be certain dose-response relationship.Control group also can suppress Na
+-K
+The reduction of-ATP enzyme.
Experimental example 5: the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule is to the influence of U-9889 rat model organs and tissues pathological change
Experimental technique:
1, the preparation of sciatic nerve electron microscope specimen: get rat sciatic nerve, fix with 2.5% glutaraldehyde, 0.1M phosphoric acid buffer (pH7.2-7.4) rinsing 3 times, each 5 minutes, 1%OSO4 (PH7.4) is 20min fixedly, 0.1M phosphoric acid buffer rinsing 3 times, ethanol-acetone gradient dehydration, the Epon812 resin embedding, 700A ultrathin section(ing), transmission electron microscope are observed sciatic pathological change down.
2, sciatic nerve histological stain: get rat sciatic nerve, use formalin fixed, paraffin embedding, do HE dyeing after the section respectively and observe the general pathological change of nervous tissue: the dyeing of Weil method selects normal myelin, new silver impregnation method dyeing to select the distortion myelin, and axon is observed in anti-silver nitrate method dyeing; The capillary blood vessel basilar membrane is selected in the dyeing of 6 amine silver, observes microvascular pathological change in neural axis, myelin and the nerve.
3, eye and nephridial tissue dyeing: get rat left eye ball and left kidney, use formalin fixed, paraffin embedding is made the dye pathological change of tissues observed of HE respectively after the section.
Experimental result:
1, HE dyeing: visible renal glomerulus and uriniferous tubules on the kidney HE staining section, control rats glomerular epithelium cell marshalling rule, renal cells is marshalling also, and uriniferous tubules is arranged evenly.The atrophy of model group kidney of rats bead is full of a large amount of exudates in the renal capsule, degree is extruded into renal glomerulus on one side, glomerular epithelium cell arrangement disorder, and renal cells swelling, even with tube chamber sealing, uriniferous tubules arrangement disorder.Visible renal glomerulus atrophy is full of a large amount of exudates on the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20mg/kg dosage group HE staining section in the renal capsule, and renal capsule increases, exudate is with fluffy of little cyst wall, glomerular epithelium cell arrangement rate is random, and renal cells swelling degree is lighter than model group, the uriniferous tubules arrangement disorder.See glomerular epithelium cell mild swelling on the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 40mg/kg dosage group HE staining section, renal capsule does not ooze out, and renal capsule increases, and renal cells swelling degree is lighter than model group.The pathological change of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 80mg/kg dosage group obviously alleviates, the slight swelling of messangial cell, and renal capsule does not ooze out, and the degree of renal cells swelling obviously alleviates.See the renal glomerulus atrophy on the control group group rat HE karyomit(e), be full of a large amount of exudates in the renal capsule, glomerular epithelium cell arrangement disorder, renal cells swelling, uriniferous tubules arrangement disorder.
Tunica fibrosa, choroid and the retina on visible eyeground on the wall of eyeball HE staining section.Each confluent monolayer cells marshalling rule of control rats wall of eyeball.The tunica fibrosa on model group rat eyeground, each the confluent monolayer cells swelling of choroid and retina, iuntercellular is full of a large amount of exudates, and choroid and amphiblestroid thickness are obviously increased.The tunica fibrosa on Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20mg/kg dosage group eyeground, each the confluent monolayer cells swelling of choroid and retina, iuntercellular is full of a large amount of exudates, and choroid and amphiblestroid thickness also obviously increase.The tunica fibrosa on Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 40mg/kg dosage group eyeground, choroid and amphiblestroid thickness increase slightly.The tunica fibrosa on Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 80mg/kg dosage group eyeground, choroid and retina cell's queueing discipline almost be can't see cellular swelling and are oozed out.The tunica fibrosa on control rats eyeground, choroid and retina cell's queueing discipline, each confluent monolayer cells mild swelling of choroid and retina, iuntercellular is full of exudate, and choroid and amphiblestroid thickness increase.
Visible sciatic nerve axon and intranueral capillary blood vessel in HE dyeing place, it is clear, neat that control rats sciatic nerve square section epineural bundle coating, single nerve fiber are arranged, the axon of nerve fiber is dyed dark-brown, and the myelin of axon outside is dyed lightpink, and uniform coloring is clear.Intranueral blood vessel is also high-visible, does not see pathologic lesion.Model group rat nerve fiber arrangement disorder, the atrophy of part fiber axon, even disappear, the part axon separates with myelin, occurs cavity in the nerve fiber, part swelling distortion.As seen wall of micrangium is thicker, vascular occlusion.Visible nerve fiber swelling distortion in Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20mg/kg dosage group HE dyeing place, matter between myelin swelling extruding neural axis reaches, oedema between also visible myelin and the epilemma, pathological change is lighter than model group and low dose group, the indivedual nerve fiber mild swelling distortion of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule high dose group, oedema in the visual field between a rarely seen nerve fiber myelin and the tunica fibrosa, most of nerve fibers is not seen pathological change.Visible nerve fiber swelling distortion on the control group group rat sciatic nerve HE staining section, matter between myelin swelling extruding neural axis reaches, also visible oedema of not counting between myelin and the epilemma.Observe the sciatic nerve sample on the painted profile of HE, it is clear, neat, tight that the control rats nerve fiber is arranged, and the axon of nerve fiber is dyed dark-brown, and the myelin of axon outside is dyed lightpink, and axon and myelin uniform coloring are clear.Schwann cell nuclear is high-visible, does not see obvious pathologic lesion.The disorder of U-9889 rat model sciatic nerve profile epineural fibre array, the atrophy of part fiber axon, even disappear, the part axon separates with myelin, occurs cavity in the nerve fiber, part fiber swelling distortion.Visible cotton-wool sample day shift in the myelin, healthy tissues is can not see in the full visual field.Visible nerve fiber swelling distortion on the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule low dose group longitudinal section, matter between myelin swelling extruding neural axis reaches oedema occurs between also visible myelin and the epilemma, and bubble sample exudate sporadically appears.Dosage group rat nerve fiber mild swelling distortion in the Radix Et Rhizoma Fagopyri Tatarici total flavone capsule, matter between myelin swelling extruding neural axis reaches, faintly visible cotton-wool sample day shift in the myelin, its pathological change is lighter than model group, it is clear, neat, tight that Radix Et Rhizoma Fagopyri Tatarici Radix Et Rhizoma Fagopyri Tatarici total flavone capsule high dose group rat nerve fiber is arranged, and axon and myelin uniform coloring are clear.Indivedual nerve fiber mild swelling distortion, the cotton-wool sample changes disappearance in the myelin.Cavity appears in visible nerve fiber swelling distortion on the control rats sciatic nerve longitudinal section in the nerve fiber, part fiber swelling distortion, bending.Matter between myelin swelling extruding neural axis reaches is also seen the oedema between minority myelin and the epilemma.
2, normal myelin staining: adopt Weil method selectivity to dye normal myelin, control rats sciatic nerve square section epineural axon is not painted, myelin is dyed black-and-blue, it is clear, neat that black-and-blue, the single nerve fiber of myelin ovalization is arranged, the myelin uniform coloring is clear, and intranueral blood vessel is also high-visible.Model group rat nerve fiber arrangement disorder, myelin is smudgy, myelin swelling, visible olistherozone territory in the myelin.The control rats nerve fiber is arranged clearly, neat, tight on the profile, and myelin sheath remained is dyed black-and-blue, and the myelin uniform coloring is clear, and the sections and the Lang Fei of myelin are high-visible, do not see obvious pathologic lesion.Cavity appears in the disorder of U-9889 rat model sciatic nerve profile epineural fibre array in the nerve fiber, be dispersed in most irregular olistherozones territory.Can see the olistherozone territory at neurospongium sheath position in Weil method dyeing place of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20mg/kg dosage group, myelin is painted irregular, and its pathological change is similar to model control group.Obviously reduce in the olistherozone territory at Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 40-80mg/kg group Weil method staining section epineural myelin position, and myelin is painted still irregular, and Lang Fei is high-visible, and neural myelin position still has a small amount of olistherozone territory, and myelin is painted very irregular; Myelin is painted irregular on the Weil method staining section of control group, and the olistherozone territory of neural myelin is less, but visible segmental and be dispersed in the olistherozone territory.
3, distortion myelin staining: adopt the new silver staining of sex change myelin send out with normal neural myelin dye light brown, selectivity is dyed black with the sex change myelin, neural axis is not painted.On the control rats sciatic nerve square section but the root nerve fiber arrange clear, neat, the myelin uniform coloring is clear.Horizontal type group rat nerve fiber arrangement disorder, myelin is smudgy.The arrangement of control rats nerve fiber is clear, neat, tight on the profile, normal neural myelin is dyed light brown, the disorder of axle urea mycin rat model sciatic nerve profile epineural fibre array, show the thread affair of black that intermittently increases the weight of, the myelin position is dispersed in irregular olistherozone territory, myelin staining is inhomogeneous, and the myelin pathology takes place in prompting.Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 20mg/kg dosage group can be seen the black pigmented section at neurospongium sheath position, and myelin is painted irregular.There is the black filament at Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 40-80mg/kg group staining section epineural myelin position, and the myelin position is dispersed in irregular olistherozone territory, and there is a small amount of olistherozone territory at the neural myelin of high dose group position, and myelin is painted very irregular; Control group group myelin is painted irregular, visible waviness black filament.
4, axon dyeing: adopt the dyeing of anti-nitre silver method to observe axon, that neural axis is dyed is brown, myelin is dyed light brown.It is clear, neat that the control rats nerve fiber is arranged, the myelin uniform coloring.Model group rat nerve fiber arrangement disorder, axon and myelin are all smudgy, myelin swelling, visible olistherozone territory in the myelin, the nerve fiber obscure boundary of swelling.The control rats nerve fiber is arranged clearly, neat, tight on the profile, and normal neural myelin is dyed light brown, and the axon traveling is parallel, the axon uniform coloring, and myelin density is even.Visible many places bulk exudate squeezes axon and myelin chaotic on the profile of model group rat nerve fiber, axon thickness inequality, and the painted depth does not wait, myelin and nerve fiber obscure boundary.Radix Et Rhizoma Fagopyri Tatarici Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 40-80mg/kg dosage group can be seen neural axis thickness inequality, the smart place of axon than the thick 2-3 of normal axon doubly, the swelling of prompting axon, axon is painted to deepen and shallowly not to wait, myelin and nerve fiber obscure boundary, there is the olistherozone territory at the myelin place.Radix Et Rhizoma Fagopyri Tatarici Radix Et Rhizoma Fagopyri Tatarici total flavone capsule 40-80mg/kg group staining section epineural axon thickness inequality, as seen axon swelling, the painted also depth of axon does not wait, myelin and nerve fiber obscure boundary, and there is the olistherozone territory at the myelin place, how much rope swelling the neural myelin of high dose group position has, the painted depth of axon does not wait, and exudate squeezes axon and myelin chaotic, myelin and nerve fiber obscure boundary, there is the olistherozone territory at the myelin place, and the feature of its pathological change is similar with model group.
5, thank to electron microscopic observation thoroughly: observe the interior microfilament queueing discipline of sciatic nerve axon of rats in normal control group under the Electronic Speculum, do not ooze out around the axon or myelin extruding sign.The density of myelin is even, and each flaggy of myelin is arranged closely rule, does not ooze out between myelin and the axon.The schwann cell form is normal.The sciatic nerve axon distortion of model group rat, the axon that has is very smudgy, is penetrated the thing extruding diameter is diminished, and has around the microfilament arrangement disorder in the axon, axon to ooze out or myelin extruding sign.The density unevenness of myelin is even, and flaggy is peeled off, and each layer myelin arrangement disorder is tangled skein of jute shape, and myelin strips off, and the myelin that has partly strips off, and has between myelin and the axon and oozes out.The schwann cell kytoplasm has liquefaction dissolving zone, presents vacuolar degeneration.The neural state of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule medication group rat is significantly better than model control group, low dosage Radix Et Rhizoma Fagopyri Tatarici total flavone capsule group axon queueing discipline, and myelin has part to strip off, and the part of myelin has flaggy to separate to observe.Have between the myelin flaggy and ooze out, the myelin exudate makes the obvious chap of myelin, the also visible vacuolar degeneration of schwann cell.Middle dosage Radix Et Rhizoma Fagopyri Tatarici total flavone capsule group axon queueing discipline, myelin have part to strip off, and there is the flaggy separation phenomenon part of myelin.The myelin flaggy has and oozes out, the visible slight vacuolar degeneration of schwann cell.High dosage Radix Et Rhizoma Fagopyri Tatarici total flavone capsule group axon queueing discipline, most myelin density are even, myelin flaggy queueing discipline, indivedual myelins have flaggy separation phenomenon slightly.The schwann cell form is normal substantially.Control group group axon queueing discipline, myelin have part to strip off, and there is the flaggy separation phenomenon part of myelin.Have between the myelin flaggy and ooze out, the control group neural state significantly is better than model control group.
Experimental example 6: Radix Et Rhizoma Fagopyri Tatarici determination of total flavonoids
The preparation of typical curve: take by weighing control substance of Rutin 30.07mg, with 30% dissolve with ethanol to the 100ml volumetric flask, get 1ml respectively, 2ml, 4ml, 6ml, 8ml in 5 25ml volumetric flasks, is supplemented to 12.5ml with 30% ethanol, NaNO2 (1: the 20) solution that adds 0.7ml, shake up, behind the placement 5min, add 0.7ml Al (NO3) 3 (1: 10) solution, add 5ml 1mol NaOH behind the 6min, shake up, to scale, measure in wavelength 500nm place behind the 10min with 30% alcohol dilution, reagent is blank reference, and the result is as follows:
| Rutin concentration C (g/L) | 0.01203 | ?0.02406 | ?0.04811 | ?0.07217 | ?0.09622 |
| Absorbance A | 0.144 | ?0.287 | ?0.572 | ?0.852 | ?1.127 |
Regression equation; C=0.0856A-0.0005 R=0.9999
The preparation of trial-product: get the about 30mg of Radix Et Rhizoma Fagopyri Tatarici total flavones, the accurate title, decide, and to the 100ml volumetric flask, gets 5ml with 30% dissolve with ethanol, puts in the 25ml volumetric flask, adds to 12.5ml with 30% ethanol, adds the NaNO of 0.7ml
2In (1: 20) solution, shake up, add the Al (NO of 0.7ml behind the placement 5min
3)
3In (1: 10) solution, behind the placement 6min, add in the 1mol NaOH solution of 5ml, shake up, to scale, measure in wavelength 500nm place behind the 10min with 30% alcohol dilution, reagent is blank reference, and by regression equation calculation content, recording the Radix Et Rhizoma Fagopyri Tatarici content of total flavone can reach more than 95%.
Embodiment 1: the extracting method of Radix Et Rhizoma Fagopyri Tatarici total flavones
Get duck wheat shell, be ground into meal, add 8 times of water, be heated to 90 ℃, slowly adding sodium hydroxide solution under agitation condition, is 8.5 until water transfer decocting liquid pH value, and lixiviate is 40 minutes with this understanding, suction filtration while hot, residue is the same to add 4 times of water treatments once again, while hot suction filtration, merging filtrate adds hydrochloric acid soln under 70 ℃, be 5 until water transfer decocting liquid pH value, stir the back standing over night, suction filtration, throw out wash with water to neutrality,, drying gets Radix Et Rhizoma Fagopyri Tatarici total flavones crude product; Get the water that this crude product adds 3 times of amounts, stirring and evenly mixing, hydro-oxidation soda solution, until water transfer decocting liquid pH value is 8, adds equivalent ethanol again, stir about 2 hours, filter, filtrate adds hydrochloric acid soln, is 5 until water transfer decocting liquid pH value, fully be heated with stirring to 80 ℃, left standstill suction filtration 10 hours, precipitation washes with water, discard washings, drying promptly gets purified Radix Et Rhizoma Fagopyri Tatarici total flavones.
Embodiment 2: the extracting method of Radix Et Rhizoma Fagopyri Tatarici total flavones
Get the Radix Et Rhizoma Fagopyri Tatarici herb, comprise Radix Et Rhizoma Fagopyri Tatarici stem, leaf, be ground into meal, add 6 times of water, be heated to 90 ℃, under agitation condition, slowly add sodium hydroxide solution, until water transfer decocting liquid pH value is 8.5, and lixiviate is 40 minutes with this understanding, while hot suction filtration, residue is the same to add 4 times of water treatments once again, suction filtration while hot, merging filtrate, adding hydrochloric acid soln down at 70 ℃, is 5 until water transfer decocting liquid pH value, leaves standstill after the stirring 24 hours and suction filtration, throw out washes with water to neutrality, the dry Radix Et Rhizoma Fagopyri Tatarici total flavones crude product that gets; Get this crude product and add 3 times of water gagings, stirring and evenly mixing, hydro-oxidation sodium solution, adjust pH is 8, adds equivalent ethanol again, stir about 2 hours, filter, filtrate adds hydrochloric acid soln, and adjust pH is 5, fully be heated with stirring to 80 ℃, leave standstill about 10 hours suction filtration, precipitation washes with water, discard washings, drying promptly gets purified Radix Et Rhizoma Fagopyri Tatarici total flavones.
Embodiment 3: the extracting method of Radix Et Rhizoma Fagopyri Tatarici total flavones
With the Radix Et Rhizoma Fagopyri Tatarici herb, promptly comprise Radix Et Rhizoma Fagopyri Tatarici stem, Radix Et Rhizoma Fagopyri Tatarici leaf, the duck wheat shell powder becomes meal; Add in the percolator, add pH value and be 12 NaOH solution, solubilization 1 ‰ S-WATs in alkaline solution again, slowly diacolation when the detection percolate does not have chromocor compound, stops diacolation; Percolate adds HCl solution, transfers pH to 4.5; Standing over night, filtration, drying get Radix Et Rhizoma Fagopyri Tatarici total flavones crude product; Dissolve with ethanol with 60% concentration refluxed 1 hour again, and crystallization is separated out in filtered while hot, cooling, and drying gets purified Radix Et Rhizoma Fagopyri Tatarici total flavones.
Embodiment 4: the extracting method of Radix Et Rhizoma Fagopyri Tatarici total flavones
With the Radix Et Rhizoma Fagopyri Tatarici herb, promptly comprise Radix Et Rhizoma Fagopyri Tatarici stem, Radix Et Rhizoma Fagopyri Tatarici leaf, duck wheat shell, powder becomes meal; Add in the refluxing extraction device, adds the alcohol reflux 3 hours of 4 times of amount 60% concentration, the extracting liquid filtering decompression recycling ethanol is not distinguished the flavor of to there being alcohol; Deepfreeze spends the night, and separates out crystallization, and filtration, drying get Radix Et Rhizoma Fagopyri Tatarici total flavones crude product; Add 3 times in water, stirring and evenly mixing slowly adds alkaline solution, is 8 until water transfer decocting liquid pH value; Add equivalent ethanol or methyl alcohol again, stir about 2 hours filters; Filtrate adds acid solution, and water transfer decocting liquid pH value is 5, fully is heated with stirring to 80 ℃, leaves standstill 10 hours, filters; Precipitation washes with water; Discard washings, drying promptly gets purified Radix Et Rhizoma Fagopyri Tatarici total flavones.
Embodiment 5: the extracting method of Radix Et Rhizoma Fagopyri Tatarici total flavones
With the Radix Et Rhizoma Fagopyri Tatarici herb, promptly comprise Radix Et Rhizoma Fagopyri Tatarici stem, Radix Et Rhizoma Fagopyri Tatarici leaf, the duck wheat shell powder becomes meal; Add 7 times of water gagings, decoct to extract 2 times, each 2 hours, united extraction liquid, extracting solution were behind high speed centrifugation, and surveying when being evaporated to 50 ℃ of relative densities is 1.20; Concentrated solution refrigeration is spent the night, and separates out crystallization, filters, and drying gets Radix Et Rhizoma Fagopyri Tatarici total flavones crude product; Add 3 times in water, stirring and evenly mixing slowly adds alkaline solution, and adjust pH is 8, stirs, and filters; Filtrate adds acid solution, and adjust pH is 5, fully stirs, and is heated to 80 ℃, leaves standstill 12 hours, filters; Precipitation washes with water, discards washings, and drying promptly gets purified Radix Et Rhizoma Fagopyri Tatarici total flavones.
Embodiment 6: the extracting method of Radix Et Rhizoma Fagopyri Tatarici total flavones
With the Radix Et Rhizoma Fagopyri Tatarici herb, promptly comprise the Radix Et Rhizoma Fagopyri Tatarici stem, the Radix Et Rhizoma Fagopyri Tatarici leaf, duck wheat shell, powder becomes meal; Add 5 times of amount methyl alcohol, refluxing extraction 3 hours; Extracting solution is put to room temperature, and gradation adds gac, stirs, leave standstill, when checking that with hydrochloric acid-magnesium powder reaction supernatant liquor does not have flavones and reacts till; Filter, collect the gac of absorption glycosides, use boiling water successively, the methyl alcohol that boils, 7% phenol solution, 15% phenol-alcoholic solution carries out wash-out; The each several part elutriant is carried out qualitative examination, identify with PPC, flavonoid glycoside can be with 7% phenol-washing down; Elutriant concentrates through reduction vaporization, removes residual phenol with the ether jolting again, and remaining water layer concentrating under reduced pressure promptly gets the Radix Et Rhizoma Fagopyri Tatarici total flavones; Add 4 times ethanol, heated and stirred 2 hours is filtered, and leaves standstill 15 hours, filters, and filtrate adds acid solution, and adjust pH is 5, fully is heated with stirring to 80 ℃, leaves standstill 10 hours, filters; Precipitation washes with water, discards washings, and drying promptly gets purified Radix Et Rhizoma Fagopyri Tatarici total flavones.
Embodiment 7: the preparation of Radix Et Rhizoma Fagopyri Tatarici total flavone capsule
Get by purified Radix Et Rhizoma Fagopyri Tatarici total flavones 100g of the present invention, add vehicle starch 140g, dextrin 50g, fully mixing, make suitable softwood with 95% ethanol, granulate, drying, whole grain, encapsulated, make 1000, every contains bitter 100 milligrams of the wheat total flavoness of supporting of effective ingredient.The oral dosage of medicine capsule of the present invention is each 1-3 grain, every day 2-3 time.
Embodiment 8: the preparation of Radix Et Rhizoma Fagopyri Tatarici total flavones tablet
Get refining Radix Et Rhizoma Fagopyri Tatarici total flavones 100g, add vehicle starch 140g, dextrin 50g by the present invention, abundant mixing, make suitable softwood with 95% ethanol, granulate drying, whole grain, add and add auxiliary material sodium starch glycolate and Magnesium Stearate, mixing, compressing tablet, make 1000, every contains bitter 100 milligrams of the wheat total flavoness of supporting of effective ingredient.The oral dosage of medicine capsule of the present invention is each 1-3 sheet, every day 2-3 time.
Embodiment 9: the preparation of Radix Et Rhizoma Fagopyri Tatarici total flavones granule
Get refining Radix Et Rhizoma Fagopyri Tatarici total flavones 100g by the present invention, add vehicle Icing Sugar 5Kg, dextrin 4Kg, fully mixing is made suitable softwood with 95% ethanol, granulate, place boiling-bed drying fluidized drying or 60 ℃ of dryings, whole grain, packing, make 1000 bags, every bag contains bitter 100 milligrams of the wheat total flavoness of supporting of effective ingredient.The oral dosage of medicine capsule of the present invention is each 1-2 bag, every day 2-3 time.
Embodiment 10: the preparation of Radix Et Rhizoma Fagopyri Tatarici injection of general flavone
Get refining Radix Et Rhizoma Fagopyri Tatarici total flavones 100g, add injection water 850ml, stirring and evenly mixing, the hydro-oxidation sodium solution, transferring to the pH value is 8, fully is heated with stirring to 80 ℃, make dissolving, add tween-80, filter, stir, use 10% hydrochloric acid soln, adjust pH is 7.5, add the injection water to 1000ml, filtering with microporous membrane, embedding, sterilization, packing, promptly.
Embodiment 11: contain the preparation of Radix Et Rhizoma Fagopyri Tatarici total flavones protective foods
Get by the inventive method and make extract 100g, add milk powder or bean powder 9.9Kg, abundant mixing, packing, every packed 10g makes 1000 bags, and every bag contains bitter 100 milligrams of the wheat total flavoness of supporting of effective ingredient.Protective foods oral dosage of the present invention is each 1-2 bag, every day 2-3 time.
Claims (3)
1, the application of Radix Et Rhizoma Fagopyri Tatarici total flavones in the medicine of preparation treatment diabetes merging nervous function damage.
2, application as claimed in claim 1 is characterized in that described treatment diabetes merge nervous function damage and are meant and improve nerve conduction velocity.
3, application as claimed in claim 1 is characterized in that described treatment diabetes merge nervous function damage and are meant reduction sciatic nerve sorbyl alcohol level.
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| CNB2003101129280A CN1324040C (en) | 2003-12-26 | 2003-12-26 | Medicament for treating diabetes, diabetes complication, its preparation and novel use |
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| CNB2003101129280A CN1324040C (en) | 2003-12-26 | 2003-12-26 | Medicament for treating diabetes, diabetes complication, its preparation and novel use |
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| CN1324040C true CN1324040C (en) | 2007-07-04 |
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Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101066299B (en) * | 2007-06-13 | 2010-09-22 | 薛九荣 | Extracting process and product of tartary buckwheat extract with rich tartary buckwheat flavone |
| CN104069187B (en) * | 2014-07-24 | 2016-06-01 | 劲牌生物医药有限公司 | The processing method of extraction purification tartary buckwheat flavone from Radix Et Rhizoma Fagopyri Tatarici |
| CN104855646A (en) * | 2015-05-15 | 2015-08-26 | 吉林农业大学 | Fagopyrum esculentum shell tea |
| CN104825552A (en) * | 2015-05-15 | 2015-08-12 | 吉林农业大学 | Buckwheat shell flavonoid extract and application thereof as AGEs (advanced glycosylation endproducts) inhibitor |
| CN105067814A (en) * | 2015-07-24 | 2015-11-18 | 中国科学院成都生物研究所 | Helicase hydrolysis ATP activity determination method |
| CN107898829A (en) * | 2017-09-26 | 2018-04-13 | 吉林农业大学 | Advanced glycation end products decomposition agent |
| TWI749435B (en) * | 2019-09-10 | 2021-12-11 | 大江生醫股份有限公司 | Use of compounds for enhancing expression of genes involved in cholesterol metabolism |
| CN112717003A (en) * | 2021-01-29 | 2021-04-30 | 温州大学 | Application of tartary buckwheat flavone in preparation of medicine for treating tissue injury induced by diabetes |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1410423A (en) * | 2001-09-28 | 2003-04-16 | 张杰克 | Technical method of extracting rutin |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1410423A (en) * | 2001-09-28 | 2003-04-16 | 张杰克 | Technical method of extracting rutin |
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